It has been known that contamination of pyrogen in injection solution may cause symptoms such as pyrexia and chills. In order to prevent contamination with pyrogen, pyrogen test has been conventionally employed in a process for preparation or quality control of injection solution to detect pyrogen. However, the test requires much time and labor and being very complicated (see Non-Patent Document 1).
Pyrogen is known to be mainly composed of endotoxin which constituting the cell wall of gram-negative bacteria. For detection and quantification of endotoxin derived from gram-negative bacteria, there are known endotoxin test methods based on a principle of coagulation of blood corpuscle extracts (lysate) of horseshoe crab (such as Limulus polyphemus or Tachypleus tridentatus) with endotoxin (see Non-Patent Document 2). Recently, such endotoxin test methods are more often used for detection of pyrogen instead of pyrogen test methods.
[Non-Patent Document 1] Commentary of the Japanese Pharmacopoeia Fourteenth Edition, Hirokawa Publishing Co. 2001 B-493
[Non-Patent Document 2] Commentary of the Japanese Pharmacopoeia Fourteenth Edition, Hirokawa Publishing Co. 2001 B-63